Info
🌱 來自: Huppert’s Notes
Spondyloarthritis (SpA)🚧 施工中
Spondyloarthritis (SpA)
Group of disorders with shared features of inflammatory arthritis with varying degrees of axial skeleton involvement, enthesitis (inflammation of tendon-bone insertion points), overt or subclinical intestinal inflammation, association with uveitis, and association with the HLA-B27 MHC allele.
Ankylosing spondylitis (AS)
• Pathogenesis:
- Not fully elucidated but several hypotheses exist regarding the role of the HLA-B27 risk allele, including presentation of self-peptides to CD8+ T cells and pathologic formation of oligomers that activate NK cells
• Epidemiology:
- Prevalence 0.9–1.4% in the United States, M:F = ~3:1.
- Age of onset is typically between 20–30 yr
- HLA-B27 genetics:
• Overall prevalence of HLA-B27 in Northern Europeans is 6%
• Prevalence of SpA (all categories) in HLA-B27+ individuals is 2–10%
• HLA-B27 is present in 74–90% of patients with spondyloarthritis overall and 95% of patients with ankylosing spondylitis
• Definition:
- Updated Assessment of Spondyloarthritis International Society (ASAS) nomenclature: Ankylosing spondylitis → Axial spondyloarthritis +/- radiographic sacroiliitis (“with radiographic sacroiliitis” is included only if the associated sacroiliitis is severe enough to be detected on plain film x-ray)
• Clinical features:
- Axial spine involvement:
• Begins with the sacroiliac (SI) joints in nearly all cases, presenting with pain localizing to the hip or buttock (as opposed to hip arthritis pain which typically localizes to the groin).
• Initially MRI is the most sensitive imaging modality (detects subchondral marrow edema in the SI joints). As disease progresses, damage becomes visible on PA pelvic plain film (reveals erosive changes, joint space narrowing and eventual bone joining [aka ankylosis or syndesmophytosis]).
• Following SI joint involvement, spinal involvement is typically next (causing inflammatory back pain with morning stiffness). Joint involvement usually then proceeds cranially in a continuous fashion without skip lesions.
• End stage disease in the spine = ankylosis of the vertebral facet joints and heterotopic ossification of the anterior and posterior spinal ligaments, resulting in “bamboo spine” (occurs in 10–15% of patients).
- Peripheral articular/periarticular involvement: Enthesitis may be seen at the achilles tendon or plantar fascia entheses; asymmetric oligoarthritis of the hips, knees, ankles, and shoulders; less commonly dactylitis of the toes
- Ocular: Recurrent anterior uveitis (30% of patients)
- Cardiovascular: Increased risk of CAD; aortitis may occur in <1% of patients
- Pulmonary: Restrictive lung disease may occur due to fusion of the costovertebral joints
• Diagnosis:
- ASAS Diagnostic Algorithm for Axial Spondyloarthritis: See Figure 9.4
FIGURE 9.4: Algorithm for the diagnosis or exclusion of axial spondylarthritis. Adapted from Tuaurog et al. New Engl J Med 2016;374:2563.
• Treatment:
- Continuous NSAIDs are first-line and can slow radiographic disease progression
- TNF-α inhibitors are typically started in patients with persistent symptoms or radiographic progression on NSAIDS
- Anti-IL-17a therapy with secukinumab or ixekizumab is recommended for patients with persistent symptoms after trial of one TNF-α inhibitor (e.g., without trying a different TNF-α inhibitor)
- Intra-articular glucocorticoids can be helpful for SI joint pain
- Methotrexate is NOT efficacious
IBD-associated arthritis
• Epidemiology: Occurs in 6–46% of patients with Crohn’s and ulcerative colitis (UC); disease onset can occur any time in the course of IBD
• Definition: Updated ASAS nomenclature: IBD-associated arthritis → Peripheral spondyloarthritis with IBD
• Clinical features:
- Articular – three clinical phenotypes:
• Sacroiliitis/spondylitis: Most common (25% patients). 50–75% are HLA-B27 positive. Axial disease activity does not track with enteric disease activity. Patients may be asymptomatic.
• Chronic inflammatory polyarthritis: Occurs in <5% of patients, typically involving the PIPs, MCPs, wrists, elbows, knees, shoulders and ankles. Does not track with IBD activity.
• Acute oligo or polyarthritis: Occurs in 5% of patients, typically involves the knees and tracks with IBD activity (e.g., may co-occur with an IBD flare).
- Derm: Pyoderma gangrenosum and erythema nodosum
- Ocular: Anterior uveitis
• Treatment:
- Non-biologic DMARDs sulfasalazine, azathioprine, 6-mercaptopurine and methotrexate are first-line
- TNF-α inhibitors are useful in patients who have persistent symptoms on non-biologic DMARDs. Only select agents are effective for both bowel and joint manifestations: Infliximab, adalimumab, golimumab, certolizumab pegol (etanercept not effective)
- NSAIDs are not recommended as they may worsen IBD
Psoriatic arthritis
• Epidemiology: Occurs in 7–42% of patients with psoriasis. Overall prevalence 0.3–2% in the US
• Definition: Updated ASAS nomenclature: Psoriatic arthritis → Peripheral spondyloarthritis with psoriasis
• Clinical features:
- Psoriasis precedes or co-occurs with arthritis in 90% of patients; in <10% of patients, joint disease can precede skin findings
- Clinical phenotypes (all involve inflammatory arthritis with morning stiffness, +/-erosions)
• Symmetric polyarthritis
• Asymmetric oligoarthritis
• DIP-predominant polyarthritis
• Spondyloarthritis
• Arthritis mutilans: End stage of hand polyarthritis with subluxation, ligamentous laxity, and telescoping of the phalanges
- Other peri-articular manifestations: Enthesitis of the Achilles tendons or plantar fascia is common, as is dactylitis of the toes. Nail dystrophy/nail pitting is a risk factor for joint disease and DIP-predominant disease in particular.
- Axial spine involvement: Unlike ankylosing spondylitis, which begins in the SI joints and proceeds cranially, axial disease in psoriatic arthritis may begin in the c-spine and involvement may be non-contiguous along the length of the spine
• Treatment:
- Continuous NSAIDs for non-destructive/non-severe disease
- Methotrexate is effective for pain in patients with non-severe disease who fail NSAIDs, but it does not impact radiographic progression
- TNF-α inhibitors slow radiographic damage in patients with erosive or severe disease
- Ustekinumab (anti-IL-12/23) and secukinumab (anti-IL-17a) is considered in patients who have failed two different TNF-α inhibitors
Reactive arthritis
• Pathogenesis: Preceding diarrhea (Salmonella, Shigella, Campylobacter, Yersinia) or Chlamydia trachomatis, followed by joint pain 2–6 weeks later. If sudden onset, rule-out HIV.
• Epidemiology: Prevalence of reactive arthritis after an episode of bacterial dysentery ranges from 2–33%. HLA-B27 is positive in 90% of *Yersinia-*related cases and 30–50% of cases associated with other pathogens (over-represented compared to HLA-B27 population prevalence of 6%)
• Definition: Updated ASAS nomenclature: Reactive arthritis → Peripheral spondyloarthritis with preceding infection
• Clinical features:
- Articular:
• Inflammatory non-erosive oligoarthritis with predilection for the knees, ankles, and wrists, occurring 2–3 weeks after an episode of bacterial inflammatory diarrhea (Salmonella, Campylobacter, E. coli, Shigella, Yersinia) or urethritis (Chlamydia trachomatis and Ureaplasma urealyticum)
• 90% of cases involve enthesitis of the Achilles tendon and plantar fascia (i.e., plantar fasciitis)
• Dactylitis is fairly common (40% in patients with disease triggered by Chlamydia urethritis)
• Spine involvement is uncommon, but SI joint involvement may occur in up to 20%
- Ocular: Sterile conjunctivitis (25% patients)
- Derm: Keratoderma blenorrhagicum begins as a vesicular or waxy papular rash of the palms and soles and subsequently becomes erythematous, scaly and hyperkeratotic. Circinate balanitis is a serpiginous shallow ulceration on the glans or shaft of the penis
- Genitourinary: In patients whose preceding infection was urethritis, a subsequent sterile urethritis, prostatitis, or cervicitis may persist for the duration of the illness
Treatment:
- Continuous NSAIDS are first-line. Most patients will have resolution of symptoms within 3–6 months, obviating need for further therapy
- Disease activity persisting >3–6 months can be treated with sulfasalazine or methotrexate
- Antibiotics are not typically needed, except in rare cases of demonstrated persistent infections
Crystal-Induced Arthritis
Gout
• Pathogenesis:
- Hyperuricemia above the uric acid saturation point of 6.8 mg/dL leads to crystal formation in the synovial fluid. This causes activation of the NLRP3 inflammasome in tissue macrophages/recruited monocytes, which leads to IL-1β production and PMN recruitment and ultimately results in acute joint swelling and pain.
- Hyperuricemia can occur due to uric acid under-excretion (largely due to genetic variation in renal tubular urate handling, but also CKD, thiazide/loop diuretics, pyrazinamide/ethambutol) vs. less commonly by uric acid overproduction (inborn errors of purine metabolism, hematologic malignancies).
Clinical features:
- Asymptomatic hyperuricemia: Population prevalence of hyperuricemia is approximately 20%, but 95% remain asymptomatic with no treatment required
- Acute gouty arthritis: Acute monoarticular swelling, erythema, warmth, and exquisite tenderness that peaks within 12–24 hrs of onset
• Periarticular soft tissue involvement is common (bursitis, tenosynovitis, panniculitis) and can clinically mimic a skin and soft tissue infection
• In men, the first gout attack typically occurs age 20–40 yr and >50% involve the 1st MTP. After years of disease, attacks may involve other joints (e.g., midfoot, ankles, knees, spine, or polyarticular)
• In women, the first gout attack typically occurs after menopause
- Tophaceous gout: After 10–20 yr of intermittent gout attacks and poorly controlled hyperuricemia, some patients develop tophi, which are conglomerates of uric acid crystals and inflammatory cells with a fibrous rind
• Common locations of tophi include the extensor surfaces of the elbows, distal Achilles tendon, PIPs, and ear cartilage
• Tophi may directly erode bone, cause functional impairment, or become superinfected, requiring debridement or amputation
• Diagnosis:
- Perform arthrocentesis (removal of joint fluid for analysis):
• Mandatory for larger joints (ankle, knee) to rule out infection with gram stain and culture (infection may co-exist with gout flare!). Arthrocentesis may not be feasible for midfoot or MTP flares, but localization to these sites increases the likelihood of gout
• Diagnostic gold standard is detection of needle-shaped, negatively birefringent monosodium urate crystals in the synovial fluid
- Negative birefringence: yellow when parallel to the polarizing axis
- Synovial WBC >2K cells/μL and may be >100K cells/μL with PMN-predominance
- Other lab findings:
• ↑ESR/CRP (non-specific)
• Checking serum uric acid is only sometimes useful; an elevated serum uric acid in a patient with acute monoarticular arthritis can support a diagnosis of gout, but serum uric acid may be low during an acute attack because inflammatory cytokines can reduce uric acid
• Treatment of acute flares:
- Colchicine: 1.2 mg loading dose followed 1 hr later by 0.6 mg, continued daily until flare resolves. Most effective if started within 24 hrs of symptom onset. Avoid in patients with GFR <60 mL/min.
- Prednisone: 0.5 mg/kg/day for 5 days (or longer if long-standing disease). Best for patients with CKD.
- NSAIDs: Max dose NSAID (e.g., naproxen 500 mg BID) for 5–7 days. Avoid in patients with CKD, CHF, GIB risk). Potentially a good option for relatively healthy patients with first flare.
- IL-1β blockade – Anakinra: Use for refractory flares in patients with long-standing disease and contraindications to and/or failure of other therapies used for acute flare management. Not used as maintenance therapy.
- Intra-articular glucocorticoids: Consider as monotherapy for monoarticular flares, particularly in the 1st MTP. Avoid or proceed with caution if synovial culture is pending.
- Check serum uric acid 2 wks post-flare to gauge steady-state level.
• Urate lowering therapy:
- Indications: ≥2 attacks per year; CKD2 or higher; tophaceous disease; uric acid nephrolithiasis
- Serum uric acid targets: No specific randomized controlled trials have studied the impact of different targets. ACR/EULAR recommends targeting uric acid <5mg/dL for patients with tophi and <6 mg/dL for others
- Timing: Urate-lowering therapy may be started during an acute flare as long as the patient is also on appropriate systemic anti-inflammatory therapy
- Auxiliary measures: Alcohol cessation, low purine diet (limit shellfish, red meat), avoid thiazide/loop diuretics/ASA if feasible
- Medications:
• Xanthine oxidase inhibitors: Prevent uric acid generation from upstream purine metabolites
- Allopurinol: First-line therapy; start 100mg daily (or 50mg daily if CKD) and uptitrate to max dose of 800 mg/day. Check HLA-B5801 in patients of Asian descent, as this allele is associated with increased risk of severe cutaneous adverse reactions including DRESS and SJS-TEN
- Febuxostat: 40–120 mg daily (40 mg febuxostat ~ 300 mg allopurinol)
• Uricosuric agents: Promotes renal tubular uric acid excretion. Probenecid is the most widely available agent. These agents are less potent than xanthine oxidase inhibitors as a monotherapy but can be added if needed. Avoid in patients with CKD
• Pegloticase: Recombinant uricase infused every two weeks. Indications = recurrent and/or tophaceous gout with intolerance to or failure of other therapies. 30–50% of patients develop anti-drug antibodies
• Anti-inflammatory prophylaxis during active uric acid lowering: Colchicine 0.6 mg daily, low-dose NSAID (e.g., naproxen 250 mg BID), or low-dose prednisone (5 mg daily) should be provided to prevent flares during active titration of uric acid lowering therapy, and should be continued for 3 months after reaching the serum uric acid target (6 months in patients with tophi)
Calcium pyrophosphate deposition (CPPD) arthropathies
• Pathophysiology: Calcium pyrophosphate crystals accumulate in joints with age (~50% of patients age >80 yr have detectable chondrocalcinosis). Secondary chondrocalcinosis may develop in younger patients due to systemic metabolic disturbances (e.g., chronic hypomagnesemia, hypophosphatemia, hyperparathyroidism, or hemochromatosis).
• Clinical syndromes and diagnosis:
- Asymptomatic chondrocalcinosis: Four most common locations in descending order are the knees, triangular fibrocartilage of the wrist (between ulna and carpals), pubic symphysis, and MCPs
- Pseudo-gout: Acute monoarticular arthritis with synovial fluid showing presence of rhomboid-shaped, positively birefringent crystals on polarized light microscopic analysis (blue when parallel to the polarizing axis). Synovial WBC typically >2K cells/μL
- “Pseudo-OA”: Characterized by OA-like radiographic changes (e.g., joint space narrowing, subchondral sclerosis, subchondral cysts, osteophytosis) in joints with preceding or concurrent evidence of chondrocalcinosis, often accompanied by deformity out of proportion to the duration of arthritis (knees most common; valgus deformity is suggestive)
- “Pseudo-RA”: A rare entity characterized by inflammatory polyarthritis of the wrists and MCP joints with chondrocalcinosis that is typically non-erosive and does not meet criteria for RA (occasionally low-positive Rf)
• Treatment:
- There is no therapy to dissolve CPP crystals
- Pseudo-gout flares: Management similar to gout flare; prophylaxis with colchicine 0.3 mg daily or low-dose NSAIDs (e.g., naproxen 250 mg BID) is reasonable if ≥3 attacks per year
- Pseudo-OA**:** Management similar to OA without chondrocalcinosis
- Pseudo-RA: Low-dose daily colchicine or low-dose daily NSAIDs; serial clinical/radiographic/laboratory diagnostic reassessment as patients may ultimately prove to have true RA